癌化学療法のラット前立腺におよぼす影響 --重量変化,組織学的所見,5α-水素添加酵素活性の検討--

Abstract

63日齢ウイスター系雄ラットに, 臨床的使用量に準じて1クールに相当する抗癌剤, cyclophosphamide (CPM), nitrogen mustard (NM), methotrexate (MTX), bleomycin (BLM), peplomycin (PLM), actinomycin-D (ACD), adriamycin (ADM), vincristine (VCR), vinblastine (VBL), cis-platinum (CDDP)の10種を経腹的に投与し, 体重, 前立腺, 精巣, 精巣上体, 副腎の重量変化, 前立腺組織中の5α-水素添加酵素(5α-reductase)の活性測定, および組織学的所見を検討した.1) CDDP-体重, 前立腺重量ともに有意に減少し, 前立腺組織の萎縮, 変性をきたす.5α-reductaseの障害はない.2) NM, VBL-前立腺重量のみ有意に減少, 体重は変化せず, 前立腺組織の萎縮, 変性をきたす.5α-reductaseの障害はない.3) BLM, PLM-体重, 前立腺重量ともに減少せず, 有意の5α-reductaseの障害をきたす.前立腺組織は一部に変性をきたす.4) CPM, MTX, ACD, ADM, VCR-体重, 前立腺重量, 5α-reductase活性にまったく影響をきたさない

To evaluate the effect of anticancer chemotherapeutic antigens on rat prostate, ten kinds of anticancer agents corresponding to the dose generally used for humans were intraperitoneally injected to 63-day-old Wistar rats. The anticancer agents were administered as follows: Cyclophosphamide (CPM) was used at the dose of 8 mg/kg for 7 days. Methotrexate (MTX), actinomycin-D (ACD) and cis-platinum (CDDP), 163 micrograms/kg, 8 micrograms/kg and 833 micrograms/kg for 5 days, respectively. Nitrogen mustard (NM), bleomycin (BLM), peplomycin (PLM), adriamycin (ADM), vincristine (VCR), and vinblastine (VBL), 500 micrograms/kg, 250 micrograms/kg, 170 micrograms/kg, 2.5 mg/kg, 33 micrograms/kg and 83 micrograms/kg, twice in a week, respectively. The rats were killed on the fifth day after completion of the schedule. Then, the weight of the body, the prostate, the epididymis and the adrenal gland were measured. In addition, 5 alpha-reductase activities and histological findings in the prostate were examined. For determination of 5 alpha-reductase activities, cell-free homogenate obtained from the rat ventral prostate was incubated with C14-testosterone at 37 degrees C for 30 minutes in an atmosphere of 95% of O2 and 5% of CO2. Subsequently, the metabolites from testosterone were separated and purified with thin layer chromatography using the solvent system with benzene acetone, 4:1 (v/v). 5 alpha-Reductase activity was determined with the sum of dihydrotestosterone (DHT) and androstanediol converted from testosterone and indicated as pmol product/mg protein. The 5 alpha-reductase activity was employed as a biological marker for the degree of androgenic dependency in the prostate. The results were summarized as follows. CDDP significantly reduced the weight of the body (p less than 0.001, n = 7), but not the activity of 5 alpha-reductase. NM and VBL had a specific action to reduce the weight of the prostate (p less than 0.01, n = 8) without causing loss of body weight. NM and VBL showed no influence on 5 alpha-reductase activities. The activity of 5 alpha-reductase was markedly damaged by BLM (p less than 0.05, n = 6) and PLM (p less than 0.05, n = 5). However no significant reduction was recognized in the weight of the body and the prostate. CPM, MTX, ACD, ADM and VCR were ineffectual on the body and the prostate weight and 5 alpha-reductase activities. In the histological examination, atrophy and degeneration of the glandular epithelium were revealed in the prostate treated with NM, VBL and CDDP.(ABSTRACT TRUNCATED AT 400 WORDS)